Overview

Mel DePamphilis, who heads the Section on Eukaryotic DNA Replication, studies the control of DNA replication and gene expression during mammalian development. His current work focuses on three questions: how genome duplication is restricted to once per cell division in proliferating cells; how these mechanisms are circumvented during mammalian development to allow some cells to differentiate into viable, nonproliferating polyploid cells; and how these mechanisms are related to human pathologies such as cancer. The Section recently discovered a novel role for the protein geminin in preventing DNA re-replication during mitosis and showed that suppression of geminin could be used to kill cancer cells without harming normal cells. The Section is currently using high-throughput screening technology to look for anti-geminin drugs and for other genes essential for proliferation of cancer cells, but not for normal cells. In addition, the group discovered novel roles for the transcription factor TEAD4 in regulating energy homeostasis during preimplantation development aa well as for the CDK inhibitors p57/Kip2 and p21/Cip1 and the DNA damage–response protein kinase CHK1 in triggering differentiation of trophoblast stem cells into trophoblast giant cells.